Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells.
(2004) In International Immunology 16(5). p.717-726- Abstract
- Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine... (More)
- Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine CII (bCII) (presenting a different peptide on H-2r) and ovalbumin could be efficiently presented, and blockage of cysteine proteases did not enhance antigen presentation. The enhanced CII-presentation by cysteine protease inhibition is seen mainly in LCs and not in antigen-primed B cells or macrophages. B cell and macrophage presentation of CII occur even without protease inhibition and are only to a minor extent influenced by cysteine protease inhibition. These data suggest that a LC deficiency in processing of the immune-dominant CII epitope in both CIA and RA may limit the exposure of this self-antigen to T cells, but that presentation can be overcome by modulation of the peptide proteolysis during CII processing. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/122542
- author
- Holmdahl, Meirav LU ; Grubb, Anders LU and Holmdahl, Rikard LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- International Immunology
- volume
- 16
- issue
- 5
- pages
- 717 - 726
- publisher
- Oxford University Press
- external identifiers
-
- wos:000221295100010
- pmid:15096478
- scopus:2442448511
- ISSN
- 1460-2377
- DOI
- 10.1093/intimm/dxh079
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019), Division of Clinical Chemistry and Pharmacology (013250300), Department of Dermatology and Venereology (Lund) (013006000)
- id
- 56cf344a-b49a-4ecb-a77b-b6f232741370 (old id 122542)
- date added to LUP
- 2016-04-01 11:58:19
- date last changed
- 2023-01-03 01:58:46
@article{56cf344a-b49a-4ecb-a77b-b6f232741370, abstract = {{Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine CII (bCII) (presenting a different peptide on H-2r) and ovalbumin could be efficiently presented, and blockage of cysteine proteases did not enhance antigen presentation. The enhanced CII-presentation by cysteine protease inhibition is seen mainly in LCs and not in antigen-primed B cells or macrophages. B cell and macrophage presentation of CII occur even without protease inhibition and are only to a minor extent influenced by cysteine protease inhibition. These data suggest that a LC deficiency in processing of the immune-dominant CII epitope in both CIA and RA may limit the exposure of this self-antigen to T cells, but that presentation can be overcome by modulation of the peptide proteolysis during CII processing.}}, author = {{Holmdahl, Meirav and Grubb, Anders and Holmdahl, Rikard}}, issn = {{1460-2377}}, language = {{eng}}, number = {{5}}, pages = {{717--726}}, publisher = {{Oxford University Press}}, series = {{International Immunology}}, title = {{Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells.}}, url = {{http://dx.doi.org/10.1093/intimm/dxh079}}, doi = {{10.1093/intimm/dxh079}}, volume = {{16}}, year = {{2004}}, }